title: Analogs of 5-(substituted benzylidene)hydantoin as inhibitors of tyrosinase and melanin formation.
abstract: BACKGROUND
  Many tyrosinase inhibitors find application in cosmetics and pharmaceutical products for the prevention of the overproduction of melanin in the epidermis. A series of 5-(substituted benzylidene)hydantoin derivatives 2a-2k were prepared, and their inhibitory activities toward tyrosinase and melanin formation were evaluated.
  
  
  METHODS
  The structures of the compounds were established using (1)H and (13)C NMR spectroscopy and mass spectral analyses. All the synthesized compounds were evaluated for their mushroom tyrosinase inhibition activity.
  
  
  RESULTS
  The best results were obtained for compound 2e which possessed hydroxyl group at R(2) and methoxy group at R(3), respectively. We predicted the tertiary structure of tyrosinase, simulated its docking with compound 2e and confirmed that this compound interacts strongly with mushroom tyrosinase residues as a competitive tyrosinase inhibitor. In addition, we found that 2e inhibited melanin production and tyrosinase activity in B16 cells.
  
  
  CONCLUSIONS
  Compound 2e could be considered as a promising candidate for preclinical drug development in skin hyperpigmentation applications.
  
  
  CONCLUSIONS
  This study will enhance understanding of the mechanism of tyrosinase inhibition and will contribute to the development of effective drugs for use hyperpigmentation.
authors.affiliation: College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, Republic of Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000363:Agaricales / Q000201:enzymology; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006827:Hydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008958:Models, Molecular; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*
chemical_list: D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D006827:Hydantoins; D008543:Melanins; D014442:Monophenol Monooxygenase